TITLE: Pilot Project D - Anticancer Effect of Novel Compounds Derived from Gorgonian Octocorals in the Caribbean Sea JO-LEADERS: UPRCCC - Abimael Rodriguez, Ph.D., Professor, Department of Chemistry MDACC - Yasuko Kondo, M.D., Ph.D., Assistant Professor, Neurosurgery- Research ABSTRACT In a pre-pilot study funded by the present U54 grant, we found that eupalmerin acetate (EPA), which was selected from 15 compounds derived from marine organisms in the Caribbean Sea, has significant anticancer effect on human malignant glioma cells both in vitro and in vivo. We have also demonstrated that EPA induces apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase (JNK) pathway. As a successful extension of our pre-pilot project, we have modified the structure of EPA and synthesized 10 additional EPAderived compounds to develop even more potent anticancer agents. We hypothesize that EPA or its derivatives (collectively referred to as EPAs) will show anticancer effect in malignant qlioma and leukemia cells both in vitro and in vivo. Therefore, the objectives of this pilot project are 1) to determine the anticancer efficacy and mechanisms of EPAs in malignant glioma and leukemia cells in vitro, 2) to determine the anticancer effect of the lead compounds in the animal cancer xenograft model, and 3) to examine pharmacokinetics and toxicity of the lead compounds. Relevance of Pilot Project to the Overall Priorities The goal of this proposal is to develop marine compounds isolated from the Caribbean Sea by an established scientist (UPR-Rio Piedras) into novel anticancer agents through collaboration of cancer specialists at MDACC. Our study is tightly associated with the U54 aims as the Co-leaders seek to continue building their existing partnership that started with a pre-pilot (pipeline) project.